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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

GZMK Gene

protein-coding   GIFtS: 52
GCID: GC05P054320

granzyme K (granzyme 3; tryptase II)

(Previous names: granzyme K (serine protease, granzyme 3; tryptase II) )
 Explore 13 diseases affiliated with
GZMK via our new
 Human Malady Compendium 
Biological research products
for GZMK
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Granzyme K (Granzyme 3; Tryptase II)1 2     Granzyme K2
TRYP21 2 3     Granzyme-33
Granzyme K (Serine Protease, Granzyme 3; Tryptase II)1 2     Tryptase II2
NK-Tryp-22 3     EC 3.4.21.-3
NK-Tryptase-21     Fragmentin-33
PRSS1     Granzyme-33
Fragmentin-33     EC 3.4.218
Granzyme 32     EC 3.4.21.48

External Ids:    HGNC: 47111   Entrez Gene: 30032   Ensembl: ENSG000001130887   OMIM: 6007845   UniProtKB: P498633   

Export aliases for GZMK gene to outside databases

Previous GC identifers: GC05P054483 GC05P055748 GC05P054290 GC05P054335 GC05P054355 GC05P051293


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for GZMK:
This gene product is a member of a group of related serine proteases from the cytoplasmic granules of cytotoxic
lymphocytes. Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize,
bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface
'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein
described here lacks consensus sequences for N-glycosylation present in other granzymes. (provided by RefSeq, Jul
2008)

Gene Wiki entry for GZMK


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000005.9  NC_018916.1  NT_006713.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the GZMK gene promoter:
         Max1   Elk-1   Nkx2-5   NF-kappaB   SRY   POU2F1   POU2F1a   NF-kappaB1   c-Myc   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGZMK promoter sequence
   Search SABiosciences Chromatin IP Primers for GZMK

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat GZMK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q11.2   Ensembl cytogenetic band:  5q11.2   HGNC cytogenetic band: 5q11.2

GZMK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GZMK gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P054320:  view genomic region     (about GC identifiers)

Start:
54,320,081 bp from pter      End:
54,330,398 bp from pter
Size:
10,318 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863 (See protein sequence)
Recommended Name: Granzyme K precursor  
Size: 264 amino acids; 28882 Da
Subcellular location: Secreted. Cytoplasmic granule
2 PDB 3D structures from and Proteopedia for GZMK:
1MZA (3D)        1MZD (3D)    
Secondary accessions: B2R563

Explore the universe of human proteins at neXtProt for GZMK: NX_P49863

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P49863

  • 4/6 DME Specific Peptides for GZMK (P49863) (see all 6)
     GDSGGPL  CKGDSGG  SGGPLIC  VLTAAHC 

    GZMK Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_002095.1  
    ENSEMBL proteins: 
     ENSP00000231009  

    Human Recombinant Protein Products: 
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    Novus Biologicals GZMK Protein
    Novus Biologicals GZMK Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for GZMK

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--


    GZMK for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    GZMK for domains           About GeneDecksing

    4 InterPro domains/families:
     IPR001314 Peptidase_S1A
     IPR001254 Peptidase_S1
     IPR018114 Peptidase_S1_AS
     IPR009003 Trypsin-like_Pept_dom

    Graphical View of Domain Structure for InterPro Entry P49863

    ProtoNet protein and cluster: P49863

    2 Blocks protein families:
    IPB001254 Serine protease
    IPB001314 Chymotrypsin serine protease family (S1) signature


    UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863
    Similarity: Belongs to the peptidase S1 family. Granzyme subfamily
    Similarity: Contains 1 peptidase S1 domain


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Enzyme Numbers (IUBMB): EC 3.4.21.42 EC 3.4.212 EC 3.4.21.-1

    miRNA
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    1 QIAGEN miScript miRNA Assays for microRNA that regulate GZMK:
    hsa-miR-590-3p
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    Inhib. RNA
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    Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004252serine-type endopeptidase activity IEA--
    GO:0008236serine-type peptidase activity TAS8656064


    GZMK for ontologies           About GeneDecksing



    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways  About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Granzyme Pathway
    Granzyme Pathway1.00

    1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for GZMK
        Granzyme Pathway


    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for GZMK

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    5/7 Interacting proteins for GZMK (P498633 ENSP000002310094) via UniProtKB, MINT, STRING, and/or I2D (see all 7)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000258947Q135093I2D: score=1 
    TUBB3Q135093I2D: score=1 
    HNRNPKP619783I2D: score=1 
    SETQ011053I2D: score=1 
    SSBP054553I2D: score=1 
    About this table

    Gene Ontology (GO): 1 biological process term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis IEA--


    GZMK for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    GZMK for compounds           About GeneDecksing

    EMD Millipore small molecules for GZMK:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for GZMK
    3 Novoseek chemical compound relationships for GZMK gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    serine 65.1 9 12384499 (1), 16166056 (1), 8039831 (1), 9569606 (1) (see all 8)
    arginine 17.5 1 1460416 (1)
    oxygen 0 12 18179823 (2)

    Search CenterWatch for drugs/clinical trials and news about GZMK / GRAK 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for GZMK gene: 
    NM_002104.2  

    Unigene Cluster for GZMK:

    Granzyme K (granzyme 3; tryptase II)
    Hs.277937  [show with all ESTs]
    Unigene Representative Sequence: BM918927
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000231009(uc003jpl.1) ENST00000512089

    miRNA
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    1 QIAGEN miScript miRNA Assays for microRNA that regulate GZMK:
    hsa-miR-590-3p
    SwitchGear 3'UTR luciferase reporter plasmidGZMK 3' UTR sequence
    Inhib. RNA
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    Additional cDNA sequence: 

    AK312074.1 BC035802.1 U26174.1 U35237.1 

    1 DOTS entry:

    DT.310659 

    24 AceView cDNA sequences:

    AA743283 NM_002104 U35237 U26174 AW183169 BC035802 BI908502 CD687238 
    AU184897 CD702487 AA947915 BX091409 CB987798 BI837702 BM918927 AA005382 
    AI445141 AA970854 AA699799 CB958972 CD705456 CD702028 AA935709 AA004281 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    GZMK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    See GZMK Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for GZMK

    SOURCE GeneReport for Unigene cluster: Hs.277937

    UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863
    Tissue specificity: Expressed in lung, spleen, thymus and peripheral blood leukocytes

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GZMK

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for GZMK gene from 3/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves F1N918_CHICK6
    Uncharacterized protein
    42(a)
    1 ↔ 1
    Z(15985983-15991670)
    zebrafish
    (Danio rerio)
    Actinopterygii LOC7950701 granzyme K-like 51.48(n)
    41.35(a)
      795070  XM_001335130.1  XP_001335166.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG169986
    CG134306
    (see all 49)
    --
    30(a)
    28(a)
    (see all 49)
    possible ortholog
    possible ortholog
    (see all 49)
    3L(7532160-7532936)
    2R(16437838-16439591)


    ENSEMBL Gene Tree for GZMK (if available)
    TreeFam Gene Tree for GZMK (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for GZMK gene
    PRTN32  GZMH2  PRSS572  CTSG2  CFD2  ELANE2  CMA12  AZU12  
    GZMM2  GZMB2  GZMA2  
    18/103 SIMAP similar genes for GZMK using alignment to 1 protein entry:     GRAK_HUMAN(see all similar genes):
    GZMA    CFD    DF    GZMH    TMPRSS15    KLK9
    CELA1    KLK11    KLK14    KLK8    PLAU    CTRL
    CTSG    GZMM    KLK4    PRSS2    TMPRSS11F    TRY8

    GZMK for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/218 NCBI SNPs in GZMK are shown (see all 218    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1919077561,2
    --54318268(+) ACTGGA/GATGTA 1 -- us2k10--------
    rs1144893281,2
    F,--54318287(+) CTGACG/ACCATC 1 -- us2k11Minor allele frequency- A:0.03NA 120
    rs1512846371,2
    --54318291(+) CGCCAC/TCCTGT 1 -- us2k10--------
    rs1841562431,2
    --54318644(+) GTCTAA/GGTCAT 1 -- us2k10--------
    rs1405030421,2
    --54318809(+) ATTAAG/TTTATA 1 -- us2k10--------
    rs355173061,2
    C--54318836(+) TATAGT/GATTAT 1 -- us2k11Minor allele frequency- G:0.00NA 2
    rs64502811,2
    C,F,A,--54318844(+) TATTTA/TTTATT 1 -- us2k1 tfbs39Minor allele frequency- T:0.44NA WA CSA EA 369
    rs1859310691,2
    --54318903(+) TCTGCC/TGAGCA 1 -- us2k10--------
    rs731306671,2
    C,--54319039(+) CTGATG/ACGTGA 1 -- us2k12Minor allele frequency- A:0.09WA 120
    rs1900087661,2
    --54319098(+) AAACAG/TAATCT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for GZMK (54320081 - 54330398 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for GZMK: --

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    GZMK for disorders           About GeneDecksing

    OMIM gene information: 600784    OMIM disorders: --

    13 diseases for GZMK:    About MalaCards
    large granular lymphocyte leukemia    t-cell large granular lymphocyte leukemia    pityriasis rosea    arts syndrome
    epicondylitis    lymphocytic leukemia    acute lymphoblastic leukemia    lymphoblastic leukemia
    allergic asthma    multiple sclerosis    leukemia    asthma
    melanoma

    1 disease from the University of Copenhagen DISEASES database for GZMK:
    Arts syndrome

    2 Novoseek disease relationships for GZMK gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    melanoma 13.5 1 16596996 (1)
    tumors 0 1 19201868 (1)


    Export disorders for GZMK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for GZMK gene, integrated from 9 sources (see all 44):
    (articles sorted by number of sources associating them with GZMK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning of cDNA for human granzyme 3. (PubMed id 7758581)1, 2, 3, 9 Przetak M.M.... Schmidt B.F. (1995)
    2. The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features. (PubMed id 12384499)1, 2, 9 Hink-Schauer C.... Jenne D.E. (2002)
    3. Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3. (PubMed id 8656064)1, 2, 9 Sayers T.J.... Smyth M.J. (1996)
    4. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. (PubMed id 1460416)1, 2, 9 Shi L.... Greenberg A.H. (1992)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    6. Characterization of three serine esterases isolated from human IL-2 activated killer cells. (PubMed id 3262682)1, 2 Hameed A.... Podack E.R. (1988)
    7. Ignition of p53 bomb sensitizes tumor cells to granzyme K-mediated cytolysis. (PubMed id 19201868)1, 9 Hua G....Fan Z. (2009)
    8. Granzyme K directly processes bid to release cytochrome c and endonuclease G leading to mitochondria-dependent cell death. (PubMed id 17308307)1, 9 Zhao T....Fan Z. (2007)
    9. Altered levels and molecular forms of granzyme k in plasma from septic patients. (PubMed id 17438453)1, 9 Rucevic M....Lim Y.P. (2007)
    10. Granzyme K displays highly restricted substrate specificity that only partially overlaps with granzyme A. (PubMed id 19059912)1, 9 Bovenschen N....Kummer J.A. (2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 3003 HGNC: 4711 AceView: GZMK Ensembl:ENSG00000113088 euGenes: HUgn3003
    ECgene: GZMK H-InvDB: GZMK

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for GZMK Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for GZMK gene:
    Search GeneIP for patents involving GZMK

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
    In Situ Hybridization Assays from
    Advanced Cell Diagnostics
    About This Section

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    GeneCards Homepage - Last full update: 19 Mar 2013 - Incrementals: 21 Mar 2013 , 15 Apr 2013 , 27 Apr 2013

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